ALLERGEN tion dictates the avoidance management FOCUS in each individual patient. Although ACD is not “curable,” many individuals will achieve complete remis- sion with assiduous avoidance. In this MYROXYLON PEREIRAE article, we highlight ACD and explore top relevant allergens, regional-based dermatitis presentations, topic-based (BALSAM OF PERU) dermatitis presentations and clinical tips The modern usages of Myroxylon Pereirae include 3 major applications in the and pearls for diagnosis and treatment. This article will focus on Myroxylon pharmaceutical, fragrance and flavoring industries. pereirae (MP). SHARON E. JACOB, MD MYROXYLON PEREIRAE: A BRIEF HISTORY MP, aka balsam of Peru (BOP), has remained 1 of the 5 most prevalent al- lergens detected by both the thin-layer rapid use epicutaneous (TRUE) test and the North American Contact Derma- titis Group over the last decade.6,7 No- tably, the first cutaneous allergic mani- festation was described by Mögling in 1880, well after it had been used in Eu- rope for over 300 years.8 BOP was so named because it was originally shipped to Europe from the port of Callao in Peru; however, the tree does not grow in Peru. This tree is native to present day El Salvador9 and goes by a number of other names (Table 1). The sap was so highly prized as a sacramental ointment by the Spanish clergy that a papal decree was issued in 1562 that for- bid the destruction of the balsam trees. Notably, since the times of the Incan Empire, the balsam extracts have been used to relieve bronchitis, colds, coughs, fevers and infections. The Aztecs were llergic contact dermatitis (ACD) or sustained dermatitis or progression to among the first to cultivate the tree in is an important disease that nota- a systematized presentation.2,3 their royal gardens make to compresses bly affects 14.5 million Americans The 2 main types of contact derma- with the mashed leaves to speed the A 1 10 each year. The economic impact of this titis are irritant and allergic, with ir- healing of wounds. disease is high in terms of both patient ritant contact dermatitis (ICD) being morbidity and loss of income, school the most common. ICD may occur in MODERN UTILIZATION and work, not to mention significant anyone who is exposed to an irritat- The modern usages of MP include 3 expenditures for visits to healthcare pro- ing substance with significant duration major applications in the pharmaceuti- viders and for medicaments. A correct or in significant concentrations such cal, fragrance and flavoring industries. diagnosis of ACD will improve, prevent as chronic or frequent water exposure, Notably, because of its mild bacteri- or “cure” the dermatitis and decrease abrasive cleansers, detergents and soaps. cidal action and capillary-bed stimulant overall costs to the healthcare system.1 It is important to note that ICD can at effects, MP is widely used in topical Once patch testing is performed and a times precede or be a concomitant di- medicines for wounds, burns and hem- culprit has been identified, education agnosis with ACD.4,5 ACD is a delayed- orrhoids. In the fragrance industry, MP becomes the critical intervention to en- type-IV hypersensitivity reaction that (or a cross-reacting derivative) may be sure adherence to an avoidance regimen. can occur due to a large number of used in a variety of consumer products With allergen avoidance, remission of chemicals from poison ivy to fragrances from aftershave lotions, baby diaper the dermatitis ensues. If patients are un- in shampoos. The evaluation of ACD fits salves and powders to deodorants, fra- able to comply with the avoidance regi- well with theranostic theory, as the epi- granced bathing products, hair products, men, they become at risk for recurrent cutaneous patch test diagnostic evalua- perfumes and sunscreens (Table 2). MP

® 20 March 2014 | The Dermatologist | www.the-dermatologist.com ALLERGEN FOCUS may also be found in “flavored” tobac- Table 1. OTHER NAMES FOR MYROXYLON Table 2. EXAMPLES OF PRODUCTS CONTAINING OR co, coffees and teas, and in a significant PEREIRAE CROSS-REACTING WITH MYROXYLON PEREIRAE number of foods. Balsamum peruvianim Hemorrhoidal ointment and suppositories such as Anusol (MP) THE COMPOSITION OF MYROXYLON PEREIRAE Black balsam Butt Paste (MP) MP is a dark brown, complex viscid China oil Calamine lotion fluid that is exuded from the wounded mature Myroxylon balsamum tree. El Honduras balsam Cough medicine, lozenges Salvador, the main exporter of BOP, Indian balsam Crest Whitening Expressions toothpaste (cinnamon) produces approximately 50 metric Peru balsam oil Dental cement tons annually. The vanilla and cinna- mon aroma can be attributed to the Surinam balsam Granulex wound healing ointment (MP) volatile cinnamein oils (which con- Toluifera Pereira balsam Minus-Sol sunscreen (cinnamates) tain cinnamates, eugenol and vanil- Reference: DermNet NZ. http://dermnetnz.org/dermatitis/balsam-of-peru- Xenaderm wound healing ointment (MP) lin), a combination of cinnamic acid, allergy.html. Accessed February 25, 2014. benzoyl cinnamate, benzoyl benzoate, Tiger balsam (clove oil) benzoic acid and nerodilol.11 Several be avoided by patients allergic to these Tincture of benzoin 15 potential contact allergens exist with- subgroups. In the culinary arts, they Reference: DermNet NZ. http://dermnetnz.org/dermatitis/balsam-of-peru- in MP and can be grouped into the are used for soup bases, sauces and in allergy.html. Accessed February 25, 2014. cinnamein oils, benzoic acid deriva- condiments, such as ketchup, barbeque tives and coniferin derivatives.2 and steak sauce.16 Table 3. OVERVIEW OF LOW-BALSAM While the MP extract can be found in Citrus peel from cumquats to grape- OF PERU DIET3 wound healing preparations and diaper fruits, limes and oranges may be used in Products that contain citrus fruits salves, it is not commonly added to cos- the production of marmalade, candies metic products,12 rather derivatives (eg, and garnishes. Citrus peel represents the Flavoring agents (mentholated) benzyl alcohol) or chemically related second most commonly reported food Spices (cinnamon, cloves, vanilla, curry) Chocolate Myroxylon pereirae, aka balsam of Peru, has remained 1 of the Wine, beer, vermouth 5 most prevalent allergens detected by both the thin-layer rapid Ice cream use epicutaneous (TRUE) test and the North American Contact Dermatitis Group over the last decade. Cola and spiced sodas Tomatoes and products containing tomatoes cross-reactors may be.13 Because of this, source leading to flare-up dermatitis in Chili, pizza, red sauces it is considered a marker for fragrance MP-sensitized individuals. It contains allergy. Unfortunately, for some patients, cinnamates and ferulic acid.17 Table 4. SUBGROUP COMPONENTS OF MYROXY- avoidance of fragrance alone may not Cinnamon is one of the top pro- LON PEREIRAE13,14 control their dermatitis (especially when vocateurs reported by MP-sensitive it is systematized) and a low-balsam diet patients. It specifically contains euge- Benzoic acid derivatives may be warranted.3,14 The low-balsam nol, cinnamates and benzoates.17 Cin- Cinnamates diet is based on eliminating foods high namon is used in sweet foods, such as Coniferins in MP constituents such as eugenol, cin- pastries, cereals, candies, cookies, cakes, namates, vanillin and benzoic acid de- pies and muffins. Cinnamon is used Eugenol rivatives, such as citrus fruits, tomatoes as a seasoning for savory dishes and Ferulic acid derivatives and condiments (Table 3). meats, and can also be added to teas, Vanillin Hausen et al identified distinct sub- hot chocolate and rum.17 groups of allergens in MP and suggested Chocolate contains significant Cloves are the dried flower buds of a specific screening series to more ac- amounts of the MP-derivatives: euge- Syzygium aromaticum, which contain eu- curately identify the allergic component nol, cinnamates and vanillin. It is used genol and vanillin. They are used in the specific to the patient and better guide as a sweetener, a drink and a glaze for preparation of curries, marinades, sau- avoidance2,13,14 (Table 4). chicken and is an industry in itself. Cola sage, pies, pickles and cigarettes. Clove contains the same MP-derivatives as oil is also used in synthetic vanilla.17 MYROXYLON PEREIRAE DERIVATIVES IN FOODS chocolate (namely eugenol, cinnamates Vanilla bean and/or extract are Tomatoes are the most common rele- and vanillin) and contains ferulic acid. It commonly used to flavor desserts, in vant/provocative food item that triggers is known for its use as a soda beverage, smoothies and teas and as a counter- flares in MP-sensitized patients. They where notably the MP-derivate sodium point to tomatoes and chili peppers in contain eugenol, cinnamates, ferulic benzoate is added as a preservative and Latin cuisine.17 Vanilla contains vanillin acid and coniferyl alcohol and should also as a marinade for meats.17 and benzoic acid.

® March 2014 | The Dermatologist | www.the-dermatologist.com 21 ALLERGEN FOCUS American Contact Dermatitis Group patch test SENSITIZATION AND TESTING TO at which the immune system meets its results: 2009 to 2010. Dermatitis. 2013;24(2):50-59. MYROXYLON PEREIRAE metaphorical “threshold” and subse- 8. Mögling R. Urticiaria durch Peru balsam. Berl The 3 most commonly reported sites quent exposures can lead to elicitation Klin Wschr. 1880;17:557-558. of MP-induced dermatitis are the hands, of a cutaneous response.24 Just as repeat- 9. Amado A, Taylor JS. Balsam of Peru or balsam face and anogenital regions. That said, it ed contact over time led to this immune of El Salvador? Contact Dermatitis. 2006;55(2):119. 10. Monardes N. Primera y segunda y tercera par- has been reported in association with an response, repeated avoidance of the ma- tes de la historia medicinal de las cosas que se traen 8 MP-anti-scabetic ointment and leg ul- jority of exposures over time will be re- de nuestras Indias occidentales qui sirven en me- cerations.18 Furthermore, an increasing quired to induce remission. dicinal. Drugs from the West Indies used in Medicine. number of ACD reactions to MP have Avoidance of specific allergens in per- Seville, Spain; 1574. been seen in infancy and childhood, sonal care products can prove to be a te- 11. Hjorth N. Eczematous allergy to balsams, al- lied perfumes, and flavoring agents, with special likely due to an increased use of per- dious task; however, there are programs reference to balsam of Peru. Acta Dermatol Venereol fumes and baby care products contain- available to aid in this endeavor. Both Suppl (Stockh). 1961;41(suppl 46):1-216. ing fragrances.19,20 the Contact Allergen Management 12. Api AM. Only Peru Balsam extracts or dis- Patch testing for MP allergy can be Program, a service offered through the tillates are used in perfumery. Contact Dermatitis. accomplished with the commercially ACDS,25 and the Contact Allergen Re- 2006;54(3):179. 13. Hausen BM, Simatupang T, Bruhn G, Evers available patch test device (TRUE Test, placement Database, developed by Mayo P, Koenig WA. Identification of new allergenic 26 Smartpractice USA) or through stan- Clinic, allow for a provider to enter a constituents and proof of evidence for coniferyl dard comprehensive testing systems (Al- patient’s known contact allergens, and benzoate in Balsam of Peru. Am J Contact Dermat. lergeaze and Dormer). produce a “shopping list” of products 1995;6(4):199-208. Cross-reactions with MP may oc- void of those particular chemicals. The 14. Hausen BM. Contact allergy to balsam of Peru. II. Patch test results in 102 patients with selected cur to colophonium (rosin), fragrance programs also can exclude cross-reac- balsam of Peru constituents. Am J Contact Dermat. mix 1, balsam of Tolu, wood and coal tors. Additionally, education for patients 2001;12(2):93-102. tars, resorcin monobenzoate, turpen- can be accessed through online pro- 15. Srivastava D, Cohen D. Identification of the tine, propolis, coniferyl benzoate and grams, such as mypatchlink.com27 and constituents of balsam of peru in tomatoes. Der- benzoin (Table 2). Occupations at risk through the ACDS website. n matitis. 2009;20(2):99-105. 16. Foodfacts.com. http://www.foodfacts.com. for sensitization include dentists (den- Accessed February 25, 2014. tal cement), bakers (flavoring agents), Dr. Jacob, the Section 17. Scheman A, Rakowski EM, Chou V, Chhatri- beekeepers (to beeswax), painters (tur- Editor of Allergen Focus, wala A, Ross J, Jacob SE. Balsam of Peru: past and pentine), violinist (rosin) and laboratory is a Pediatric Contact future. Dermatitis. 2013;24(4):153-160. technicians (fixatives used in the prepa- Dermatitis Specialist at 18. Saap L, Fahim S, Arsenault E, et al. Con- tact sensitivity in patients with leg ulcer- ration of histology slides). Rady Children’s Hospital ations: a North American study. Arch Dermatol. – UCSD in San Diego, 2004;140(10):1241-1246. PRACTICALS OF PATCH TESTING Sharon E. Jacob, MD CA. 19. Herro EM, Matiz C, Sullivan K, Hamann C, As discussed, patch testing is of- Jacob SE. Frequency of contact allergens in pedi- ten necessary to confirm the diagnosis Disclosure: Dr. Jacob is an investigator for the atric patients with atopic dermatitis. J Clin Aesthet safety and efficacy trial of the SmartPractice Dermatol. 2011;4(11):39-41. of ACD and to identify the relevant Thin-layer Rapid Use Epicutaneous (TRUE) Test in 20. Fisher AA. Perfume dermatitis in children sen- children and adolescents. allergen(s) responsible. Screening patch sitized to balsam of Peru in topical agents. Cutis. test trays are available, which isolate the 1990;45(1):21-23. most common chemicals and offer the References 21. allergEAZE Allergens website. http://www. provider clues for potential sources. The 1. Bickers DR, Lim HW, Margolis D, et al. The allergeaze.com/allergens.aspx?ID=Series. Ac- burden of skin diseases: 2004 a joint project of the cessed on February 25, 2014. American Contact Dermatitis Society American Academy of Dermatology and the So- 22. Patch Test Products 2011. Chemotechnique (ACDS) Standard Series includes 80 ciety for Investigative Dermatology. J Am Acad of Diagnostics. 2011. http://www.chemotechnique. allergens from several different catego- Dermatol. 2006;55(3):490-500. se/. Accessed on February 25, 2014. ries,21 additional supplemental trays are 2. Hsu JW, Matiz C, Jacob SE. Nickel allergy: lo- 23. Nijhawan RI, Jacob SE. Patch testing: the also available.22 When it comes to MP, calized, id, and systemic manifestations in children. whole in addition to the sum of its parts is great- Pediatr Dermatol. 2011;28(3):276-280. est. Dermatitis. 2009;20(1):58-59. patch testing with the constituents and 3. Salam TN, Fowler JF Jr. Balsam-related sys- 24. Jacob SE, Herro EM, Taylor J. Contact derma- cross-reactors may increase the chance temic contact dermatitis. J Am Acad Dermatol. titis: diagnosis and therapy. In: Elzouki AY, Harfi of demonstrating a relevant positive 2001;45(3):377-381. HA, Nazer HM, Bruder Stapleton F, Oh W. Whit- reaction and allow for more specific 4. Nijhawen RI, Matiz C, Jacob SE. Contact der- ley RJ, eds. Textbook of Clinical Pediatrics. 2nd ed. avoidance instructions.23 matitis: from basics to allergodromes. Pediatric An- New York, NY: Springer; 2012. nals. 2009;38(2):99-108. 25. ACDS CAMP. American Contact Dermatitis 5. Militello G, Jacob SE, Crawford GH. Allergic Society website. http://www.contactderm.org/ PEARLS OF TREATMENT: EVERY DOSE COUNTS contact dermatitis in children. Curr Opin Pediatr. i4a/pages/index.cfm?pageid=3489. Accessed Feb- A person might be exposed to and 2006;18(4):385-390. ruary 25, 2014. subsequently sensitized to a contact al- 6. Krob HA, Fleischer AB Jr, D’Agostino R Jr, 26. Contact Allergen Replacement Database web- lergen (eg, a fragrance) for days to years Haverstock CL, Feldman S. Prevalence and rel- site. http://www.preventice.com/card/. Accessed evance of contact dermatitis allergens: a meta- February 25, 2014. before demonstrating the clinical pic- analysis of 15 years of published T.R.U.E. test data. 27. Balasam of Peru. MyPatchLink website. ture of ACD. With each exposure, there J Am Acad Dermatol. 2004;51(3):349-353. http://www.mypatchlink.com/pdf/Balsam_Peru. is an increased risk of reaching a point 7. Warshaw EM, Belsito, DV, Taylor JS, et al. North pdf. Accessed February 25, 2014.

® 22 March 2014 | The Dermatologist | www.the-dermatologist.com